For the purpose of carrying out smoothly enzymatic reaction of water-insoluble substrates in organic solvents, a new type of immobilized enzyme, a lipid-lipase aggregate, was developed. In order to prepare various kinds of lipid-lipase aggregates, 27 kinds of dialkyl ether-type phospholipid analogues were newly synthesized and used for the preparation of aggregates with lipase. Thus obtained lipid-lipase aggregates catalyzed effectively an asymmetric hydrolysis of water-insoluble (<plus-minus>)-alpha-acyloxy ester in water-saturated isopropyl ether producing (S)-alpha-acyloxy ester, a key intermediate for medicinally active diltiazem hydrochloride, much more efficiently than lipase immobilized with synthetic prepolymer (ENTP-400) in water-saturated isopropyl ether. Namely, the reaction time became much shorter (2 to 3d for completion as compared with 21d) and the chemical and optical yields of the reaction products were found to be high. An ether-linked lipid-lipase aggregate obtained by sonication treatment was considered to have stacked bilayr structure of the lipid in the crystalline phase based on X-ray diffraction analysis. In addition, for the purpose of the synthesis of chiral synthon using lipase, a facile chemoenzymatic route to optically active 4,5-disubstituted-2E-hexenoate derivatives was achieve